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FOXA1: A Pioneer of Nuclear Receptor Action in Breast Cancer

Darcie D Seachrist1,2, Lindsey J Anstine2,3, Ruth A Keri1,2,4,5

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Cancers
|October 23, 2021
PubMed

Insights

FOXA1 regulates estrogen-responsive genes in breast cancer. Its interaction with other nuclear receptors influences endocrine therapy response and resistance, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • FOXA1 is crucial for estrogen-responsive transcriptomes in luminal breast cancer.
  • Dysregulated FOXA1 impacts estrogen receptor (ER) activity, driving endocrine resistance.

Purpose of the Study:

  • To review FOXA1's regulation of nuclear receptor (NR) function in breast cancer.
  • To explore NR interplay in endocrine resistance and therapeutic strategies.

Main Methods:

  • Literature review of FOXA1's role in breast cancer.
  • Analysis of NR crosstalk and its impact on ER transcriptional programs.

Main Results:

  • FOXA1 regulates multiple NRs (androgen, glucocorticoid, progesterone) beyond ER.
  • NRs reprogram FOXA1-ER cistromes, influencing endocrine therapy outcomes.
  • NR interplay is key to endocrine therapy response and resistance.

Conclusions:

  • FOXA1's multifaceted role in NR regulation impacts breast cancer progression.
  • Understanding NR crosstalk offers therapeutic vulnerabilities for endocrine-resistant breast cancer.
Keywords:
FOXA1androgen receptorbreast cancerendocrine resistanceestrogen receptorglucocorticoid receptornuclear receptorsprogesterone receptor

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